Invited Faculty
  • Akihiro Ishizu
    Hokkaido Univ.
    Japan
  • We have focused on the involvement of neutrophils extracellular traps (NETs) in the pathogenesis of ANCA-associated vasculitis (AAV). NETs are DNA fibers released extracellularly by activated neutrophils and are decorated with antibacterial proteins derived from the neutrophil cytoplasm. This is an essential innate immune system, but excessive NETs bring disadvantages to the living body. Currently, in AAV, the following facts have been demonstrated: 1) serum factors such as ANCA induce NETs [1], 2) the activity of DNase I, which is a physiological degradation factor of NETs, is decreased, resulting in the accumulation of NETs in the tissues [1], 3) NETs resistant to DNase I are formed locally in the lesion [2], and 4) NETs that remain in the lesion without being degraded disrupts immunological tolerance to the ANCA antigens, which are components of NETs, resulting in the induction of ANCA production [3]. Based on these findings, we have proposed that a vicious cycle mediated by ANCA and NETs is critically involved in the pathogenesis of AAV [4].

    References
    1. Nakazawa D, et al. J Am Soc Nephrol 25(6): 990-997, 2014. doi: 10.1681/ASN.2013060606.
    2. Masuda S, et al. Am J Pathol 189(4): 839-846, 2019. doi: 10.1016/j.ajpath.2019.01.007.
    3. Nakazawa D, et al. Arthritis Rheum 64(11): 3779-3787, 2012. doi: 10.1002/art.34619.
    4. Nakazawa D, et al. Nat Rev Rheumatol 15(2): 91-101, 2019. doi: 10.1038/s41584-018-0145-y.
    Research & Clinical Focus

    Anti-neutrophil cytoplasmic antibody

    Neutrophil extracellular traps

    Vasculitis

    Pathology

    • Date Time Room Session Title Lecture Title
    May 20 16:00-16:30 Room A [International Symposium] Vasculitis Session Recent basic studies in ANCA-associated vasculitis